Vitamin B12-dependent MTR reactions may also have neurological effects, through an indirect mechanism. Adequate methionine (which, like folate, must otherwise be obtained in the diet, if it is not regenerated from homocysteine by a B12 dependent reaction) is needed to make S-adenosyl-methionine (SAMe), which is in turn necessary for methylation of myelin sheath phospholipids. Although production of SAMe is not B12 dependent, help in recycling for provision of one adequate substrate for it (the essential amino acid methionine) is assisted by B12. In addition, SAMe is involved in the manufacture of certain neurotransmitters, catecholamines and in brain metabolism. These neurotransmitters are important for maintaining mood, possibly explaining why depression is associated with B12 deficiency. Methylation of the myelin sheath phospholipids may also depend on adequate folate, which in turn is dependent on MTR recycling, unless ingested in relatively high amounts.
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